1. Field of the Invention
Precipitate-free dialysis solutions.
2. Discussion of the Prior Art
The invention is concerned with a sodium bicarbonate containing concentrate for the production of a dialysis fluid for the cleaning of blood. In addition to the removal of metabolic products, one of the most important tasks of artificial kidney therapy such as hemodialysis, hemofiltration, hemodiafiltration, CAVH, CAVHD and peritoneal dialysis is the correction of metabolic acidosis. For this reason, all of the dialysis fluids used in these procedures contain a buffer. In hemodialysis, as well as in CAPD, bicarbonate in the form of sodium bicarbonate was the original buffer. However later, other buffers such as lactate (usually utilized in CAPD) or acetate usually used in hemodialysis, were utilized in place thereof.
In addition to the original technical problem of inability to control the stability of the dialysis fluids, a particular problem resided in the precipitation of calcium carbonate in these solutions constituted the reason for changing the buffer substance. In the therapy of uremic patients calcium concentrations of the order of 2 mmol/liter and bicarbonate concentrations up to 42 mmol/liter are utilized or required. Thus, because of the mode of utilization or addition of these solutions, the solubility product of calcium and carbonate is exceeded and thus, the precipitation of calcium carbonate from the solution takes place. The problem is aggravated by the precipitation of calcium carbonate in the CAPD solutions because, for reasons of sterility it is necessary to autoclave at approximately 120.degree. C.
In hemodialysis and procedures associated therewith, bicarbonate buffer containing dialysis solutions have for several years been provided in such a way that on the one hand the basic bicarbonate concentrate, and on the other hand the calcium ion containing acidic electrolyte concentrate were maintained in separate containers (see Feriani, et al., U.S. Pat. No. 4,630,727 of Dec. 23, 1986, the disclosure of which is incorporated herein by reference). The containers are connected to the dialysis machine and only immediately before use are the two concentrates mixed together with water to form the actual dialysis fluid. Even taking these precautions in formation of the solutions, calcium carbonate precipitation still occurs in the dialysis machines which can clearly lead to disturbances in the dialysis procedure.
In order to avoid complications in the long term, the several tubing lines of the dialysis machine are regularly washed out with acids such as acetic acid and similar dilute acids, in order to remove the calcium carbonate.
The art recognizes a plurality of patents which are concerned with the production of bicarbonate containing dialysis fluids for blood cleaning. In several publications there is disclosed the utilization of an acid concentrate and a basic bicarbonate solution wherein the pH values of both concentrates are controlled by the pH of certain introduced dissociable salts, such as calcium chloride, sodium bicarbonate or sodium carbonate. Thus, additional acid can be provided to the acid concentrate in order to raise the level of acidity, that is to say, to reduce the measured pH value to provide, after mixing with a basic concentrate, the physiological pH value of 7.3.
Arrangements for the production of a bicarbonate containing dialysis fluid, concentrate, and dialysis fluids themselves are disclosed in DE-OS 3146425, EP-OS 022922 and EP-OS 086553 as well as, in patents cited in this last reference. It is common to several of these patents that no correction of the pH of the bicarbonate containing concentrate is suggested in order to reduce or even eliminate the calcium carbonate precipitation after mixing of the calcium containing concentrate. This is explicable, since the addition of the acid is known to move the bicarbonate/carbon dioxide equilibrium into the direction of carbon dioxide which means that gaseous carbon dioxide is released. This requires particular security measures for the containers since otherwise the carbon dioxide could leak out and thus cause the pH value to rise again, that is to say, the pH is pushed into the basic region.
Thus, for chemical reasons the already acidic calcium ion containing solution is further acidified with acid in order to attain the desired dialysis fluid composition upon mixing with the bicarbonate concentrate.
As in the case of hemodialysis, following the suggestion of Feriani and LaGreca, the reintroduction of bicarbonate in place of the less physiological lactate as buffer, is separated from the calcium containing electrolyte solution in a two chambered container as is described in U.S. Pat. No. 4,630,727. Further publications of these authors are to be found in Int. Art Organs (1985) pages 57 to 58, and in the Monograph Peritoneal Dialysis Proceeding of the Second International Course (1986) pages 143 to 148. With the arrangement described in these publications, in which both concentrates may be held in two mutually connectable chambers, autoclaving can be carried out without any problems. However, a calcium carbonate precipitation after the mixing or during the treatment in the peritoneal cavity cannot be avoided since, in a relatively short time after mixing (maximum two hours) calcium carbonate does precipitate, which is not a viable proposition in peritoneal dialysis.
In order to avoid the precipitation of calcium carbonate, these authors utilized dilute aqueous sodium bicarbonate that is to say, a bicarbonate content of less than 30 mmol/liter and a calcium concentration of 1.5 mols/liter in the final solution. Apart from the fact that this approach does not deal with the danger of precipitation, these bicarbonate concentrations are insufficient to adequately correct acidosis of the patient. Thus, the bicarbonate plasma level of the patients does not rise above 22 mmol/liter and usually remained below this level, while the normal bicarbonate plasma level should be of the order of 25 mmol/liter. The task of the invention therefore, is to provide a bicarbonate concentrate and a process for preparing a bicarbonate containing dialysis fluid wherein the danger is avoided that calcium carbonate precipitation occurs during the mixing step or during the time of dialysis treatment.